Colorectal Carcinoma

Presented by-Dr.Prabhu Dayal Sinwar

Guide –Dr . S.P.CHOUHAN

Occurs in three formHereditary Sporadic Familial•Family history•Younge age at oncet•Presence of other specific tumors and defects

•20%FAP-1%HNPCC-5%FCC-10-15%

•Absence of family history•Generally affect older population[60-80yr age]•Isolated colon or rectal lesion

•80%

•Increased risk in which index case is young[<50yr age]•Relative is close[first degree relative]

Risk factor• Age [m/c]• Dietary factor

• High animal fat diet• Low fiber diet• Alcohol

• Hereditary syndrome• FAP - germ line APC mutation –accelerated tumor

initiation, 100% risk of CRC• HNPCC-germ line mutation in MMR gene –accelerated

tumor progression,70-80% life time risk of CRC

• Inflammatory bowel disease eg. UC,Crohns ds.

• Streptococcus bovis bacteremia• Uretero sigmoidostomy• Smoking• Acromegaly• Pelvic irradiation

dietary fiber,Vegetables,Fruits,antioxidant vitamins,NSAIDS,Selenium,Calcium,Hormone replacement therapy

decreased risk

Pathogenesis

Normal colonic epithelium

Dysplastic aberrant crypt

foci

Early adenomas

Intermediate adenomas Late adenomas Carcinomas Metastasis

FAP[Familial Adenomatous Polyposis]

APC truncation mutation B-catenin level raise Wnt activatedcyclin D1 and Myc overexpresioncell proliferation and tumor formation

FAP cont….

• Autosomal dominant• >100 adenomatous polyp• 5q21 chromosome• <1% all CRC• Periampulary ca duodenumExtra intestinal featuresOsteomas, desmoid tumor,CHRPE,medulloblastoma[Gardner syn; Turcot syn.]

• Diag. – APC gene testing• Rx- prophylactic proctocolectomy with IPAA

Carcinogenesischromosome instability pathway

HNPCC[Hereditary non polyposis colon cancer]

mismatch repair (microsatellite instability) pathway

HNPCC• Autosomal Dominant• Chromosome 2[hMSH2,hMSH6], 3[hMLH1], 7[hPMS2] {MMR

gene}• 3-5% of all CRC• Poorly differentiated & mucinous• Signet ring histologyLynch I-CRC onlyLynch 2-CRC with asso. Malignancy

• Endometrial• Gastric • Ovarian• Muri-Torre synd.

Diag.– Family history– detection of germ line mutation in MMR

Clinical criteria for HNPCCAmsterdam criteria

At least three relative with colon cancer – One is the first degree relative of other two– Two successive generation– One case diagnose before 50 yr age– FAP excluded

Modified Amsterdam criteria– All above with asso. Of HNPCC (other malignancy)

Bethesda criteriaAmsterdam criteria OR one of the following– Two cases of HNPCC – asso cancer in one patient including synchronous or

metachronous cancer – Colon cancer and a first degree relative with HNPCC asso cancer and/or

adenoma– Colon or endometrial cancer diagnosed before age 45 yr– Right side colon cancer that have undifferentiated pattern or signet cell

histopathology– Adenomas diagnosed before 40 yr

Screening recommendation

• FAP– Colonoscopy annually– Beginning at age 10-12yr

• HNPCC– Colonoscopy

– every 2 yr beginning age 20yr– Annually after age 40yr or 10yr younger than earliest case in

family

Colorectal polypNeoplastic polyp

incidenceRisk of malignancy

Non neoplastic polyp

Adenomatous polyp /adenomas

1. Tubular2. Tubulovillous3. villous

65-80%10-25%5-10%

5%20%40%

1. Hyperplastic2. Hamartomatous

Cowden's dsFamilial juvenile polyposisPeutz jeghers synd.Ruvalcaba –myhre-smith synd.

3. Inflammatory

Site of Carcinoma

Rectum-38%{M/C}Sigmoid colon-21%Caecum-12%

Transverse colon -5.5%Ascending colon-5%Descending colon-4%

Splenic flexure-3%[L/C]

Clinical feature

Right colon

1. Fungating / cauliflower growth

2. Ulcerative lesion leading to chronic insidious blood loss

MelenaFatigueAbdominal pain

3. Good prognosis

Left colon

1. Annular, constricting or stenosing growth

2. Symptom of obstructionChange in bowel habbit

3. Poor prognosis

Diagnosis

1. Abdominal and Per-rectal examination2. Fecal occult blood testing[FOBT]3. Barium enema4. Water soluble contrast enema- to establish

anatomical level of obstruction5. Colonoscopy[gold standard] and sigmoidoscopy6. biopsy7. Virtual colonoscopy

8. MRI-better in rectal ca9. Ultrasound- trans rectal10. CECT abdomen and pelvis11. FDG-PET12. serum markers (elevated blood levels of

carcinoembryonic antigen)13. molecular detection of APC mutations in epithelial

cells, isolated from stools14. tests under development: detection of abnormal

patterns of methylation in DNA isolated from stool cells

Haggit classification for polyp containing cancer

• Acc. To depth of invasionLevel o

Level 1

Level 2

Level 3

Level 4

NOT invade muscularis mucosa

Invade but limited to head of polyp

Level of neck of polyp

Any part of stalk

Invade sub mucosa but above muscularis propria

Staging

Staging

• TNM staging-Primary tumor-• Tx-cannot be assessed• To-no evidence of primary tumor• Tis-carcinoma in situ-intraepithelial or invasion of lamina

propria• T1- tumor invade sub mucosa• T2-muscularis propria• T3-into peri colorectal tissue• T4a-penetrate surface of visceral epithelium• T4b-invade or adherent to other organ or structure

Regional lymph node-• Nx-• N0-• N1-one to three• N1a-one• N1b-two to three• N2-four or more• N2a-four to six• N2b-seven or more

Distant metastasis• Mo-• M1-distant metastasis• M1a-confined to one organ or site• M1b-more than one organ or site or

peritoneum

Modified Dukes classificationstage description

A

B1

B2

C1

C2

D

confined to bowel wall

partially penetrate the muscularis propria

Fully…………………………………………………………

Lymph node invasion without penetration of entire bowel wall

…………………………………with……………………………………………..

Distant metastasis

Systemic Metastasis

• Incidence related to the depth of invasion• Liver > lung

Hepatic Extra hepatic

•5-10 % undergo curative liver resection with upto 50% long term survival•Synchronous metastasis have poor prognosis•Recurrence is common•CEA testing every 3mt for 2yr after hepatic resection

•Pulmonary metastasis•Ovarian metastasis

Treatment

• Surgical resection the only curative treatment

• Likelihood of cure is greater when disease is

detected at early stage

• Early detection and screening is of pivotal

importance

Treatment according to stage• Stage 0[Tis,No,Mo]

• Stage1[T1,N0,M0]Malignant polyp

• Stage1&2[T1-3,N0,M0]Localised colon ca

• Stage3[any T,N1,Mo]Lymph node metastasis

• Stage4[Tany,Nany,M1]Distant metastasis

Endoscopic polypectomy

Segmental colectomy

Surgical resection

Surgical resection + adjuvant chemo

Metastetectomy+chemo

• Right hemicolectomy Caecum, ascending colon, hepatic flexure

•Extended right hemicolectomy

Transverse colon lesion

•Left hemicolectomy Tumor of descending colon

•sigmoidectomy Sigmoid colon tumor

•Abdominal colectomy [subtotal/total]

Multiple primary tumor, HNPCC, occasionaly in completely obstructing sigmoid cancer

Indication of chemo therapy

• Stage2 with at least one poor prognostic indicator eg.– Insufficient lymph node sampling[<12 node

resected]– T4 lesion– Poor differentiated histology– Bowel perforation

• Stage3• Stage4

• Chemotherapy regimen-– FOLFOX[5-FU, Leucovorin, Oxaliplatin]

• Newest agent-effective for metastatic disease– Cetuximab ,Panitumumab-EGFR inhibitor– Bevacizumab-VEGF inhibitor

Prognosis

• Most important guide to prognosis is STAGE of the disease i.e. depth of penetration and number of LNs involved

ADVERSE C/F1. Younger age < 30 yr2. Long symptomatology3. Obstruction/ perforation4. Location-pelvic and splenic

flexure

• ADVERSE PATHOLOGY

1. Disease stage

2. High grade

3. Colloid/ Signet ring cell-mucin production

4. Venous Invasion

5. Perineural invasion

6. Aneuploidy

7. ↑↑ CEA/ collagen

8. Diminished stromal immune reaction

9. P53 gene mutation

5 yr survival following treatmentStage Survival

1 90%

2 75%

3 50%

4 <5%

Follow up

• Stage 1-– Colonoscopy 1yr after operation then every 5yr– CEA level –every 3mt during first 2yr

• Stage 2-– CEA level every 3mt for 2yr, every 6mt for a total

of 5yr– Annual CT scan of abdo and chest for 3yr

Ca Rectum• Share many genetic, biological, and

morphologic characteristic of colon ca• Age of presentation >55yr• Bleeding is earliest and most common

symptom• Other sym.-

– Sense of incomplete defecation– Tenesmus and spurious diarrhea– Bloody slime

Diagnosis

• Rigid sigmoidoscopy and biopsy• TRUS• Endorectal coil MRI• CECT

TreatmentStage o [Tis, No, Mo] Local excision

Stage 1[T1-2,No,Mo] PolypectomyRadical resection

Stage 2[T3-4,No,Mo] Pre op chemo radiation + radical resection

Stage 3[Tany,NoMo] Pre op chemo radiation + radical resection

Stage 4 [Tany,NanyM1]

Palliative procedure

• Low anterior resection– >5cm above dentate line

• Abdomino perineal resection– At or below 5cm from dentate line

• Hartmann's procedure– For elderly or severely unstable pt

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